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Cited by 29Stress Responses and CortisolPosttraumatic Stress Disorder ResearchChild Abuse and Trauma

The roles of comorbidity and trauma exposure and its timing in shaping HPA axis patterns in depression

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Mayer, Stefanie E., Peckins, Melissa, Kuhlman, Kate R., Rajaram, Nirmala, Lopez-Duran, Nestor L., Young, Elizabeth A., Abelson, James L.·2020·Psychoneuroendocrinology
DOI 10.1016/j.psyneuen.2020.104776PMC PMC7502500
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Abstract

Background Much work has documented hypothalamic pituitary adrenal (HPA) axis abnormalities in major depressive disorder (MDD), but inconsistencies leave this system's role in the illness unclear. Comparisons across studies are complicated by variation in co-morbidity (Posttraumatic Stress Disorder-PTSD, anxiety disorders), exposure to trauma, and timing of trauma (child vs. adult). Here, we examined the impact of these factors on HPA axis profiles in depression. Methods We recruited 5 groups of participants: MDD (n = 14), comorbid MDD + PTSD following adulthood trauma (MDD + PTSD-Adult; n = 12), comorbid MDD + PTSD following childhood trauma (MDD + PTSD-Child; n = 18), comorbid MDD + social anxiety disorder (MDD + SAD; n = 12), and non-depressed control participants who were sex and age matched to patients (combined total n = 36). HPA axis function was assessed using three challenges: stress reactivity via the Trier Social Stress Test (TSST), feedback sensitivity via a dexamethasone suppression test (DST), and central drive via a metyrapone challenge (MET). We compared hormonal responses between patient groups and their respective non-depressed controls. Results MDD + PTSD-Child showed low cortisol levels at baseline, and reduced adrenocorticotropic hormone (ACTH) levels at baseline and throughout the TSST. MDD-only, MDD + PTSD-Adult, and MDD + SAD did not differ from non-depressed controls in HPA axis responses to the TSST. Controlling for childhood trauma severity, the reduced baseline levels in MDD + PTSD-Child were no longer significant and significantly reduced baseline cortisol levels emerged for MDD + PTSD-Adult. No diagnostic group effects were detected with DST and MET. Childhood maltreatment subtypes were associated with unique HPA axis responses to TSST and MET. Conclusion Comorbidity and trauma exposure, as well as their timing and type, contribute to inconsistencies in the depression literature and must be included in efforts to clarify the role of the HPA axis in MDD.

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  • No baseline cortisol differences were found in either children or adults with comorbid MDD and PTSD.

    “A further study investigating differences in baseline cortisol in patients with comorbid psychiatric illnesses found no baseline cortisol differences in either children or adults with comorbid MDD and PTSD (155).”

    From Childhood Trauma, the HPA Axis and Psychiatric Illnesses: A Targeted Literature Synthesis (2022) · cites this paper as [155]

    The TSST Results report lower baseline cortisol in the MDD+PTSD-Child group than in matched controls, contrary to the claim of no difference. The MDD+PTSD-Adult group showed no unadjusted difference, but lower baseline cortisol emerged after adjustment for childhood trauma. Here, “Child” and “Adult” refer to the timing of trauma, not the patients’ ages. (LLM, conf=0.91)

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  • When HPA axis feedback was measured through metyrapone challenge, no differences in cortisol levels were found.

    “When HPA axis feedback was measured through metyrapone challenge, no differences in cortisol levels were found (155).”

    From Childhood Trauma, the HPA Axis and Psychiatric Illnesses: A Targeted Literature Synthesis (2022) · cites this paper as [155]

    The Methods (Statistical Analysis, MET; page not supplied) state that patients and matched non-depressed controls did not differ in cortisol suppression during the metyrapone challenge. However, the Discussion identifies metyrapone as a test of central drive, not HPA-axis feedback; it identifies the dexamethasone suppression test as the measure of feedback sensitivity. (LLM, conf=0.88)

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  • Lower cortisol and ACTH responses were shown following the TSST in children with comorbid MDD and PTSD; adults with PTSD commencing in adulthood and those with social anxiety disorder showed no differences.

    “Lower cortisol and ACTH responses were shown following the TSST in children with comorbid MDD and PTSD; however, adults with PTSD commencing in adulthood and those with social anxiety disorder (SAD) showed no differences.”

    From Childhood Trauma, the HPA Axis and Psychiatric Illnesses: A Targeted Literature Synthesis (2022) · cites this paper as [155]

    The Methods (Participant Recruitment and Evaluation; page unavailable) exclude participants under 18: “MDD+PTSD-Child” refers to adults whose trauma and PTSD began in childhood, not children with MDD and PTSD. The Results (TSST Results; page unavailable) report lower baseline cortisol and lower ACTH during the TSST in that group, but not a lower cortisol response over time. They also report no TSST differences from matched controls for the MDD+PTSD-Adult and MDD+SAD groups; the SAD finding is specific to patients with comorbid MDD. (LLM, conf=0.91)

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Authors
Mayer, S. E., Peckins, M., Kuhlman, K. R., Rajaram, N., Lopez-Duran, N. L., Young, E. A., & Abelson, J. L.
Affiliations
  • University of California, San Francisco (US)
  • St. John's University (US)
  • University of California, Los Angeles (US)
  • University of Michigan (US)
Corresponding author
Mayer, Stefanie E.
ORCID
Venue
Psychoneuroendocrinology
Publisher
Elsevier BV
Published
2020-10
Volume
120
Pages
104776
ISSN
0306-4530 (ISSN-L)
DOI
10.1016/j.psyneuen.2020.104776
PMC
PMC7502500
OpenAlex
W3036068788
Cited by
29
References
14
Citations by year
2026: 6 · 2025: 3 · 2024: 7 · 2023: 2 · 2022: 7 · 2021: 2 · 2020: 1 · 2019: 1
FWCI
1.73
Type
journal article
Language
en
Open access
Licence
Locations
  • Psychoneuroendocrinology (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institutes of Health
Topics
  • Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
  • Social Sciences › Psychology › Clinical Psychology › Posttraumatic Stress Disorder Research
  • Social Sciences › Psychology › Clinical Psychology › Child Abuse and Trauma
Keywords
major depressive disorder, hypothalamic-pituitary-adrenal axis, comorbidities, post-traumatic stress disorder, childhood trauma, adult trauma, social anxiety disorder, cortisol, ACTH, stress reactivity, dexamethasone suppression test, Trier Social Stress Test
MeSH terms
Adverse Childhood Experiences, Adrenocorticotropic Hormone, Adult, Anxiety Disorders, Depression, Depressive Disorder, Major, Major Depressive Disorder, Dexamethasone, Female, Humans, Hydrocortisone, Hypothalamo-Hypophyseal System, Male, Pituitary-Adrenal System, Stress Disorders, Post-Traumatic, Comorbidity

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